In-line sensors for dialysis applications

ABSTRACT

A system for monitoring water quality for dialysis, dialysis fluids, and body fluids treated by dialysis fluids, is disclosed. The system uses microelectromechanical systems (MEMS) sensors for detecting impurities in input water or dialysis fluid, and in the prepared dialysate. These sensors may also be used to monitor and check the blood of the patient being treated. These sensors include ion-selective sensors, for ions such as ammonium or calcium, and also include amperometric array sensors, suitable for ions from chlorine or chloramines, e.g., chloride. These sensors assist in the monitoring of water supplies from a city water main or well. The sensors may be used in conjunction with systems for preparing dialysate solutions from water for use at home or elsewhere.

BACKGROUND

This patent relates generally to medical fluid delivery systems andmethods. More particularly, this patent discloses systems, methods andapparatuses for microelectromechanical systems (MEMS) sensors forsensing and measuring species in fluids involved in dialysis, such asperitoneal dialysis fluid, hemodialysis fluid, and blood.

Due to various causes, a person's renal system can fail. Renal failureproduces several physiological impairments and difficulties. The balanceof water, minerals and the excretion of daily metabolic load is nolonger possible and toxic end products of nitrogen metabolism (urea,creatinine, uric acid, and others) can accumulate in blood and tissue.

Kidney failure and reduced kidney function have been treated withdialysis. Dialysis removes waste, toxins and excess water from the bodythat would otherwise have been removed by normal functioning kidneys.Dialysis treatment for replacement of kidney functions is critical tomany people because the treatment is life saving.

Hemodialysis and peritoneal dialysis are two types of dialysis therapiesused commonly to treat loss of kidney function. A hemodialysis (“HD”)treatment utilizes the patient's blood to remove waste, toxins andexcess water from the patient. The patient is connected to ahemodialysis machine and the patient's blood is pumped through themachine. Catheters or needles are inserted into the patient's veins andarteries, or an artificial graft so blood can flow to and from thehemodialysis machine. The blood passes through a dialyzer of themachine, which removes waste, toxins and excess water from the blood.The cleaned blood is returned to the patient. A large amount ofdialysate, for example about 120 liters, is consumed to dialyze theblood during a single hemodialysis therapy. Hemodialysis treatment lastsseveral hours and is generally performed in a treatment center aboutthree or four times per week.

Another form of kidney failure treatment involving blood ishemofiltration (“HF”), which is an alternative renal replacement therapythat relies on a convective transport of toxins from the patient'sblood. This therapy is accomplished by adding substitution orreplacement fluid to the extracorporeal circuit during treatment(typically ten to ninety liters of such fluid). That substitution fluidand the fluid accumulated by the patient in between treatments isultrafiltered over the course of the HF treatment, providing aconvective transport mechanism that is particularly beneficial inremoving middle and large molecules.

Hemodiafiltration (“HDF”) is another blood treatment modality thatcombines convective and diffusive clearances. HDF uses dialysate to flowthrough a dialyzer, similar to standard hemodialysis, providingdiffusive clearance. In addition, substitution solution is provideddirectly to the extracorporeal circuit, providing convective clearance.

Peritoneal dialysis uses a dialysis solution, referred to as dialysate,which is infused into a patient's peritoneal cavity via a catheter. Thedialysate contacts the peritoneal membrane of the peritoneal cavity.Waste, toxins and excess water pass from the patient's bloodstream,through the peritoneal membrane and into the dialysate due to diffusionand osmosis, i.e., an osmotic gradient occurs across the membrane. Thespent dialysate is drained from the patient, removing waste, toxins andexcess water from the patient. This cycle is repeated.

There are various types of peritoneal dialysis therapies, includingcontinuous ambulatory peritoneal dialysis (“CAPD”), automated peritonealdialysis (“APD”), tidal flow APD and continuous flow peritoneal dialysis(“CFPD”). CAPD is a manual dialysis treatment. The patient manuallyconnects an implanted catheter to a drain, allowing spent dialysatefluid to drain from the peritoneal cavity. The patient then connects thecatheter to a bag of fresh dialysate, infusing fresh dialysate throughthe catheter and into the patient. The patient disconnects the catheterfrom the fresh dialysate bag and allows the dialysate to dwell withinthe peritoneal cavity, wherein the transfer of waste, toxins and excesswater takes place. After a dwell period, the patient repeats the manualdialysis procedure, for example, four times per day, each treatmentlasting about an hour. Manual peritoneal dialysis requires a significantamount of time and effort from the patient, leaving ample room forimprovement.

Automated peritoneal dialysis (“APD”) is similar to CAPD in that thedialysis treatment includes drain, fill, and dwell cycles. APD machines,however, perform the cycles automatically, typically while the patientsleeps. APD machines free patients from having to manually perform thetreatment cycles and from having to transport supplies during the day.APD machines connect fluidly to an implanted catheter, to a source orbag of fresh dialysate and to a fluid drain. APD machines pump freshdialysate from a dialysate source, through the catheter, into thepatient's peritoneal cavity, and allow the dialysate to dwell within thecavity, and allow the transfer of waste, toxins and excess water to takeplace. The source can be multiple sterile dialysate solution bags.

APD machines pump spent dialysate from the peritoneal cavity, though thecatheter, to the drain. As with the manual process, several drain, filland dwell cycles occur during APD. A “last fill” may occur at the end ofCAPD and APD, which remains in the peritoneal cavity of the patientuntil the next treatment.

Both CAPD and APD are batch type systems that send spent dialysis fluidto a drain. Tidal flow systems are modified batch systems. With tidalflow, instead of removing all of the fluid from the patient over alonger period of time, a portion of the fluid is removed and replacedafter smaller increments of time.

Continuous flow, or CFPD, systems may clean or regenerate spentdialysate instead of discarding it. The systems pump fluid into and outof the patient, through a loop. Dialysate flows into the peritonealcavity through one catheter lumen and out another catheter lumen. Thefluid exiting the patient passes through a reconstitution device thatremoves waste from the dialysate, e.g., via a urea removal column thatemploys urease to enzymatically convert urea into ammonia. The ammoniais then removed from the dialysate by adsorption prior to reintroductionof the dialysate into the peritoneal cavity. Additional sensors areemployed to monitor the removal of ammonia. CFPD systems are typicallymore complicated than batch systems.

In each of the kidney failure treatment systems discussed above, it isimportant to monitor and control the composition of the dialysis fluid,including the water used to make the dialysis fluid. The purity of theincoming water is obviously important. In home situations, there istypically no control or monitoring of the water from a city main or froma person's well. Once the dialysis fluid is made, it may be useful to atleast check its complete composition, at least to insure that the properfluid is being used. At present this cannot be done without taking asample to a lab for testing and analysis. If more than one type of fluidis being used for peritoneal or other dialysis treatment, it may beuseful to check the composition of each container, to insure that theproper containers have been procured and are connected correctly to theperitoneal dialysis machine.

Dialysis fluid may be used in more than one pass, i.e., hemodialysisfluid may be routed more than once through the dialyzer before it isfiltered or purified and peritoneal dialysis fluid may also be used inmulti-pass therapies. There is at present no easy way to monitor thecomposition of the fluid before the first pass, or after the first orsecond pass, short of taking a sample and sending it to a laboratory foranalysis. Using a plurality of standard sensors at one or more points inthe fluid circuits would be very expensive and would also occupy spacethat is not available at the bedside of the patient, whether in ahome-care or even in an institutional-care setting.

SUMMARY

There are many embodiments of the present invention, in which MEMSsensors are used to sense and quantify analytes of interest in dialysisfluid and in water for use in dialysis fluid. The MEMS sensors areuseful in dialysis fluid intended for both peritoneal dialysis andhemodialysis.

In a first embodiment of the present invention, a system for preparingdialysis fluid is provided. The system includes a first purificationvessel which includes a purification medium for water, and a device forpumping or measuring the water. The system also includes a heater forheating the water and a mixing chamber configured for receiving waterfrom the device and for mixing the water with a concentrate to form afresh dialysis solution. A filter for filtering the fresh dialysissolution is provided, as well as a microelectromechanical systems (MEMS)sensor that is placed in fluid communication with an output from avessel selected from the first purification vessel, the heater, themixing chamber and the filter.

In a second embodiment of the present invention, a system for preparingdialysis fluid is provided. The system includes a first purificationcartridge that includes a purification medium for water, and alsoincludes a heater for heating water received from the first purificationcartridge. The system also includes first and second pumps for pumpingand metering first and second concentrates, and a mixing chamberconfigured for receiving the first and second concentrates from thefirst and second pumps and for mixing the first and second concentrates.The mixing chamber is used to mix the water with the first and secondconcentrates to form a fresh dialysis solution. The system furtherincludes a filter for filtering the fresh dialysis solution, and amicroelectromechanical systems (MEMS) sensor placed in fluidcommunication with an output of a vessel selected from the firstpurification vessel, the heater, the mixing chamber and the filter,wherein the MEMS sensor is suitable for sensing at least two substancesin a stream selected from the group consisting of water from the firstpurification cartridge, the fresh dialysis solution and the filtereddialysis solution.

In a third embodiment of the invention, a method for preparing dialysissolution is provided. The method includes the steps of furnishing asupply of water and purifying the water in at least one pass through apurification medium. The method also includes the steps of heating thewater and adding the water to at least one dialysis concentrate to forma dialysis solution. In addition, the method includes the steps offiltering the dialysis solution and sensing at least two characteristicsof the water with a microelectromechanical systems (MEMS) sensor.

In a fourth embodiment of the invention, a method of preparing dialysissolution is disclosed. This method includes the steps of furnishing asupply of water and spent dialysate and purifying the water and thespent dialysate in at least one pass through a purification medium. Thepurification medium may be in one vessel or more than vessel, asdescribed below. The method also includes the steps of heating the waterand adding the water and at least one dialysis concentrate to form adialysis solution. In addition, the method includes filtering the formeddialysis solution and sensing at least two characteristics of a streamselected from the group consisting of the water, the formed dialysissolution and the spent dialysis solution, using a microelectromechanicalsystems (MEMS) sensor.

In a fifth embodiment, a method of purifying dialysis solution isdisclosed. The method includes the steps of furnishing a supply of spentdialysate and purifying the spent dialysate in at least one pass througha purification medium in a vessel to form a purified dialysate. Themethod also includes the steps of filtering the spent dialysate to forma filtered dialysate, and sensing at least two characteristics of astream selected from the group consisting of the spent dialysate, thepurified dialysate and the filtered dialysate. The characteristics aresensed with a microelectromechanical systems (MEMS) sensor.

Another embodiment is a method for performing dialysis. The methodincludes the steps of providing a dialysis machine and a supply ofdialysis fluid and also includes the steps of sensing and determining acomposition of the dialysis fluid with a MEMS sensor. The MEMS sensor issuitable for sensing and detecting at least two ions in the dialysisfluid. The method also includes the steps of performing dialysis on apatient using the dialysis fluid, and sensing and determining acomposition of the dialysis fluid after the step of performing dialysis,using a MEMS sensor. Additionally, the method includes the steps ofpurifying the dialysis fluid after the step of performing dialysis, andsensing and determining a composition of the dialysis fluid after thestep of purifying with a MEMS sensor. The method includes a step ofreusing the dialysis fluid if the composition of the dialysis fluidafter the step of purifying is suitable for dialysis.

Additional features and advantages are described herein, and will beapparent from the following Detailed Description and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic view of a first system for purifying water orspent dialysis solution before hemodialysis;

FIG. 2 is a schematic view of a second system for purifying water orspent dialysis solution before hemodialysis;

FIG. 3 is a schematic view of a third system for purifying water andpreparing dialysis solution, directed more to peritoneal dialysis;

FIG. 4 is a schematic view of a system for purifying water and preparingdialysis solution, especially for peritoneal dialysis;

FIG. 5 is a perspective view of a hemodialysis machine with a system fortreating, purifying, and reusing spent dialysate; and

FIG. 6 is a schematic view of a system for preparing dialysis solutionusing MEMS sensors.

DETAILED DESCRIPTION

MEMS sensors are used in embodiments of the present invention to detectand quantify analytes of interest in dialysis fluids. MEMS sensors arecapable of detecting numerous properties and species in a variety ofaqueous fluids. These fluids include water, dialysis fluid, spentdialysis fluid and even blood. The properties include pH, conductivity,temperature, oxidation-reduction potential and total hardness. Speciesinclude ammonia or ammonium, total dissolved solids (TDS), carbonate,bicarbonate, calcium, magnesium, sodium, potassium, chloride and others.

A MEMS sensor includes a substrate with a plurality of electrode sensorelements adapted to measure relevant species of an aqueous analyte. Thesensor elements include, for example, electrodes and selectivemembranes. These elements, together with any support circuitry requiredto drive the sensor element, make up the complete sensor. For example,the substrate can include a plurality of electrodes covered byion-selective membranes and an amperometric sensor including a workingelectrode and a counter electrode. In one application, the substrate,including the sensor elements, is connected to an analyzer capable ofcalculating one or more desired properties, such as the disinfectionindex of a water sample. Optionally, the substrate includes additionalsensor elements configured to measure additional species. These elementmay include an ammonia sensor, an oxygen sensor, or a sensor for amutagenic species, such as an immunosensor or a DNA probe. Sensors mayalso be used to detect and quantify additional physical properties, suchas temperature, conductivity and oxidation-reduction potential.

Exemplary sensors can be fabricated on silicon substrates. They mayalternatively be fabricated on other types of substrates such as, forexample, ceramic, glass, SiO₂, or plastic, using conventional processingtechniques. Exemplary sensors can also be fabricated using combinationsof such substrates situated proximate to one another. For example, asilicon substrate having some sensor components (e.g., sensing elements)can be mounted on a ceramic, SiO₂, glass, plastic or other type ofsubstrate having other sensor components. These other sensor componentsmay include sensing elements, one or more reference electrodes, or both.Conventional electronics processing techniques can be used to fabricateand interconnect such composite devices. These techniques are alsodescribed in U.S. Pat. No. 4,743,954 and U.S. Pat. No. 5,102,526, whichare hereby incorporated herein by reference.

The sensors can utilize micro-array sensor chip technology on a siliconplatform. For example, ion-selective electrode-based sensor elements canbe implemented in a silicon-based embodiment, such as that as describedby Brown, “Solid-state Liquid Chemical Sensors” (Miniaturized AnalyticalDevices Microsymposium, Chemistry Forum, 1998, pp. 120-126), thedisclosure of which is hereby incorporated herein by reference.Alternative silicon-based sensor devices, and the manners in which suchdevices can be fabricated, are described in U.S. Pat. No. 4,743,954(“Integrated Circuit for a Chemical-Selective Sensor with VoltageOutput”), U.S. Pat. No. 5,102,526 (“Solid State Ion Sensor with SiliconeMembrane”), and U.S. patent application Ser. No. 09/768,950(“Micromachined Device for Receiving and Retaining at Least One LiquidDroplet, Method of Making the Device and Method of Using the Device”),the disclosures of which are hereby incorporated herein by reference.The chip platform can be based on other electrochemical solid statesensor technology that is well known in the art, as shown by Brown etal. in Sensors and Actuators B, vol. 64, June 2000, pp. 8-14, thedisclosure of which is hereby incorporated herein by reference. Thesilicon chip incorporates a combination of chemically-selective sensorsand physical measurements that work in concert to deliver chemicalprofiling information on a test sample as small as one drop, and whichare also suitable for continuous, on-line sensing and monitoring offluids.

As described in U.S. Pat. Appl. Publ. 20080109175, which is herebyincorporated herein by reference, sensors for use in systems disclosedherein can be fabricated using known lithographic, dispensing and screenprinting techniques. These include conventional microelectronicsprocessing techniques. These techniques can provide sensors havingsensing elements with micro-sized features integrated at the chip level,and can be integrated with low-cost electronics, such as ASICs(application specific integrated circuits). Such sensors and electronicscan be manufactured at low cost, thereby enabling wide distribution ofsuch sensors for general use. The sensor may be a MEMS sensor as sold bySensicore, Inc., Ann Arbor, Mich., U.S.A. These sensors usemicroelectromechanical systems (MEMS) technology, that is, very smalldevices with very small components. These sensors are described innumerous patents and patent publications from Sensicore, including U.S.Pat. Nos.: 7,100,427; 7,104,115; 7,189,314; and 7,249,000, each of whichis hereby incorporated by reference in its entirety and relied upon.These MEMS sensors are also described in numerous patents pending,including U.S. Pat. Appl. Publications: 20050251366; 20060020427;20060277977; 20070050157; 20070219728; and 20080109175, each of which ishereby incorporated by reference in its entirety and relied on.

The microelectromechanical system (MEMS) sensors may be used in manyaspects of dialysis fluid preparation and processing to ensure patientsafety, comfort, economy and convenience, as well as treatment efficacy.The economy and convenience arise from the use at home of theembodiments described below, as well as many other embodiments that arenot described here, but will be obvious to those having skill indialysis arts.

FIG. 1 illustrates a first embodiment of a system 10 for preparing freshdialysis solution from spent dialysate using MEMS sensors to sense,measure, and report various characteristics of the dialysate. In thissystem, dialysis fluid enters from a source 11 of dialysis fluid, suchas the effluent from a spent dialysate pump that forms part of ahemodialysis machine. FIG. 1 depicts a plurality of sensors 13, locatedat several points around the system 10. The intent is not to suggestthat a sensor is needed at every point depicted, but rather todemonstrate the plurality of locations where a sensor may advantageouslybe placed.

Each sensor 13, as shown in the inset, includes a power source 132, suchas a battery, a sensing element 134 with a working portion 136, andoptionally, a module 138 for remote communication, such as to acontroller of the system. The power source may be furnished byelectrical wiring from a controller of the hemodialysis machine, or fromanother power source, such as a convenience outlet or a modular powersupply for a series of MEMS sensors.

Sensor element 134 is a MEMS sensor and working portion 136 includes thecircuitry necessary to process signals from the sensor and convert themto useful information. These signals may be sent to a controller of thehemodialysis machine via wired connections, or the MEMS sensor mayinclude a remote communications capability. In this embodiment, thesignal processing circuitry and wireless transmitter or radio 138 aresmall and compact, and are easily placed into the sensor housing at thesensing site. One suitable remote communications module is a wirelessmodule in accord with the ZigBee/IEEE 805.15.4 standard. This is astandard for a very low power radio system with a very limited range,about 10-20 feet. Modules made in accordance with this standard may bepurchased from Maxstream, Inc., Lindon, Utah, U.S.A., Helicomm, Inc.,Carlsbad, Calif., U.S.A., and ANT, Cochrane, Alberta, Canada. Themodules are very small and are suitable for such remote applications. Asnoted, the sensor 13 optionally includes a power supply and may alsoinclude an ADC converter to convert analog data from the sensing elementinto digital data. The digital data is thus formatted, at least by thesensor, before transmission to the controller of the hemodialysismachine or other extracorporeal processing machine controller.

MEMS sensors include sensors which may be placed in-line between onevessel and a succeeding vessel, and also include sensors which may beplaced within a vessel, such as a processing vessel or cartridge, or astorage vessel. Many MEMS sensors are capable of detecting many speciesof ions or contaminants, and some are also capable of sensing andrelaying a temperature, pH (as in hydrogen or hydronium ionconcentration), conductivity, total dissolved solids (TDS), and soforth.

Hemodialysis Applications

Returning to FIG. 1, system 10 includes a source 11 of water or spentdialysis fluid, with a MEMS sensor 13 placed at the source formonitoring characteristics of the incoming water or fluid. A firstprocessing vessel 12, such as a bed of activated carbon or charcoal, isplaced downstream of the source 11. The bed of activated carbon orcharcoal is excellent for removing a number of contaminants, includingsmall particles and also including heavy metals, chlorine, chloramines,and organics, among others. The bed of activated carbon or charcoal isrelatively non-selective in the types of contaminants removed. Ifdesired, a second processing vessel 12 or bed of activated carbon orcharcoal may be used, with a second sensor 13 placed downstream of thesecond vessel. This will allow the user time to change beds, forinstance, if a dialysis treatment is needed after the sensor for thefirst bed has indicated that the effluent is above an acceptable limitfor a particular contaminant, such as chloramine, β₂-microglobulin, orcreatinine.

After one or two beds of activated carbon or charcoal, another vessel 14for purification of the water or spent dialysate may be used, with afourth sensor downstream of vessel 14. This vessel may include anydesired purification substance, and may include a single adsorbent ormore than one layer of different adsorbents. Vessel 14 may include alayer of urease and zirconium phosphate for converting urea intoammonium ions and then removing the ammonium by forming ammoniumphosphate. Alternatively, or in addition, there may be a layer ofzirconium oxide for removing phosphates or sulfates. Vessel 14 may alsoinclude an ion exchange resin suitable for exchanging ions of wastesubstance for ions that are desirable in dialysis solutions, such ascalcium or magnesium ions, and also bicarbonate or acetate ions. The ionexchange resin may include filtering beds of carbon or charcoal beforeor after, or before and after, the resin itself. These supplemental bedsalso help to purify the final product, whether water for makingdialysate or refreshed dialysate for service to the patient.

In the embodiment of FIG. 1, once the rejuvenated dialysis fluid leavesvessel 14, it is routed to the dialysate side of a dialyzer 16, used forhemodialysis. A dialyzer may be compared to a shell-and-tube heatexchanger, with the dialysate on the shell side and the blood of thepatient running through the tube side counter-current to the dialysisfluid. In this embodiment, the dialysis fluid enters through inlet port162 and leaves through dialysis fluid outlet port 164, where anadditional MEMS sensor may sense and measure a variety of species withinthe exiting dialysis fluid. Once the dialysis fluid leaves throughoutlet port 164, it may be disposed of or may be sent again to befiltered and purified for another pass.

The other side of the dialyzer is connected to the patient's blood.Blood enters through the inlet header 166, flows through many hundred orthousand tiny porous tubes, and then leaves through the outlet header168. The tiny porous tubes allow water and toxic substances in theblood, such as creatinine and urea, to flow from the blood side to thedialysis solution side. In addition, electrolytes and bicarbonate buffermay flow from the dialysis solution side to the blood side. The cleansedblood is then sent to an air detector or air trap before returning tothe patient. An additional sensor 13 may be used to check thecomposition of the incoming blood for contaminants or other species nearinlet header 166. An additional sensor 17 may be used to check forcontaminants or other species near outlet header 168. Sensor 17 may betuned for different species than sensor 13, for example, measuring pH,phosphates or urea, may be very important to determine the condition ofthe cleansed blood as it is returned to the patient.

It is understood that other cleansing and purifying devices may be usedto purify incoming water or to cleanse spent dialysate fluid for reuse.These alternatives include filters, such as small particle filters andeven ultrafilters, such as submicron filters, for removing bacterial orendotoxin contaminants. A second embodiment of a system 20 thatadvantageously uses MEMS sensors is depicted in FIG. 2. System 20includes first and second purifying vessels 22, which may be smallcartridges rather than gallon-size vessels. A MEMS sensor 23, asdescribed above, senses and measures levels of the desired contaminantsor species, as described above.

In system 20, there is also an 5 micron filter 24 followed by areverse-osmosis filter 25, with a waste outlet 252 to drain. Thereverse-osmosis filter 27 may be equipped with a MEMS sensor 23 thatincludes a temperature sensor, for proper operation of thereverse-osmosis filter. The MEMS sensor may also include one or moresensors that monitor specific ions or substances, such as ammonia orammonium, total dissolved solids (TDS), Ca⁺⁺, Mg⁺⁺, Na⁺, K⁺, Cl⁻, and soforth. After reverse-osmosis, the system may include a UV-lightgenerator 26, wherein the light generated is cidal to bacteria and otherharmful microorganisms. Additionally, the light may be used todissociate chloride ion from nitrogen atoms in chloramine molecules,thus removing chloramines from the water or dialysis fluid. Ultravioletlight for these applications is typically UV-C, with a wavelength fromabout 180-290 nm. Lamps with a wavelength of about 185 nm or about 254nm are preferred. Without being bound to any particular theory, it isbelieved that UV light penetrates the outer cell walls ofmicroorganisms, where it passes through the cell body, reaches the DNAand alters the genetic material, and is thus cidal to the microorganism.Other desired wavelengths may be used.

An ultrafilter 27 is placed downstream of the UV light generator,followed by the dialyzer. Dialyzer 28 has a dialysis fluid inlet 282 anda dialysis fluid outlet 284, each of which may also be equipped with aMEMS sensor 23. Dialyzer 28 has a blood inlet header 286 and a bloodoutlet header 288 opposite the inlet header. The composition of theblood at the outlet may be sensed and monitored by a MEMS sensor 29 thatis tuned, as above, for a particular component or property of the bloodthat is important, such as pH, phosphate, or urea.

The patient or a caregiver may take special note of the sensor readingsfrom sensor 29 and from the last sensor 23 at the dialysis fluid outlet284. Readings of the composition or the state of the blood is importantto gauge whether the dialysis treatment is working and whether dialysisshould be continued as is or whether some modification to the patient'sprescription may be needed, whether dialysis fluid, duration orfrequency of the treatment, and so forth. Of course, a comparable resultmay also be achieved by analyzing the composition of the spent dialysisfluid, since the waste that leaves the patient's body must either remainin the dialyzer or enter the dialysis fluid. The condition of the spentdialysis fluid is thus important. If the fluid has toxic componentswithin certain high ranges, it may be expedient not to re-use any partof the fluid and to instead replace it with fresh dialysis fluid. If therange is more reasonable, a user or caregiver may decide to recycle andrefresh at least part of the spent fluid, rather than sending it todrain. The composition of the spent dialysate also provides informationon the efficacy of the dialysis therapy, albeit not as precisely asmonitoring the patient's blood. While not depicted in FIG. 2, it isunderstood that there may be one or more metering pumps or flow metersto control the flow of dialysis fluid to and from dialyzer 28 or any ofthe process vessels or cartridges upstream of dialyser 28. It should beunderstood that many of the techniques and much of the equipmentdescribed above may be applicable to both hemodialysis and peritonealdialysis applications.

Peritoneal Dialysis Applications

A system 30 designed for peritoneal dialysis is depicted in FIG. 3.System 30 accepts water or spent dialysate fluid from a source 31, suchas a water tap or an outlet from a patient yielding spent dialysate. Thesystem includes at least one vessel 32 for purifying the water or spentdialysate. In a manner similar to that described above for the othersystems, first vessel 32 may include activated carbon or charcoal, ormay include more than one layer for selectively or non-selectivelyadsorbing impurities or wastes from either water or from spent dialysisfluid. The system includes a MEMS sensor 33, as discussed above. In thissystem, the spent dialysis fluid or water is sent to a dialysis fluidpreparation system 34, of which one embodiment is described below inFIG. 6.

In one example, the dialysis fluid preparation system may simply be acontainer with a known quantity of concentrate of known composition. Forexample, system 34 may be a flexible container with a known volume(liquid) or a known mass (solid) of a known concentrate for a singlecomponent dialysis solution, e.g., a dialysis lactate solution. Adialysis lactate solution typically contains electrolytes, lactate, andglucose. The water source 31 and necessary controls, such as a controlvalve in series with the water source of the vessel 32, are used toadmit the proper amount of water to system 34, where the components aremixed and dissolved to form the desired solution. The amount of water orspent dialysate admitted may be measured, for example, by monitoring apositive-displacement pump for the fluid or water, or an accuratepositive-displacement meter in series with the in-flow Alternatively,the amount of water or fluid can be controlled by weighing the massadmitted, e.g., by placing container 34 on a weigh scale, mass cell, orother device.

It is understood that dialysis solution preparation may include heatingor pressurization, or both heating and pressurization, and hence atleast one temperature sensor or temperature element and at least onepressure sensor or pressure element may be used in the dialysis fluidpreparation. The resulting dialysis solution is checked at least onceafter its preparation by MEMS sensor 35.

In this embodiment, the fresh dialysis fluid is stored in at least onecontainer 36 and its temperature is sensed and monitored by at least onetemperature element or temperature sensor. When the dialysis fluid isneeded, it is pumped via pump 37 through a filter 38, which routes theimpurities to a drain and sends the purified filtrate to a peritonealdialysis machine 39. The contents of the fluid may be checked by anadditional MEMS sensor 35 at the input to the peritoneal dialysismachine. As is well known to those in peritoneal dialysis arts, theperitoneal dialysis machine may operate in one or more modes to routedialysis fluid to the peritoneum of the patient for a dwell period, orfor a continuous flow-through mode, or other mode. The dialysis fluidmay be routed to the patient P through the inlet lumen 391 of atwo-lumen catheter, as shown. When the dwell time is reached, or if theflow-through is continuous, the dialysis fluid is routed from thepatient through the outlet lumen 392 of a two lumen catheter. Themake-up of the spent dialysis fluid returned from the patient may bechecked by an additional MEMS sensor 33 for the parameters discussedabove.

There are other embodiments that may advantageously use MEMS sensors forthe preparation of dialysis solutions, including solutions forhemodialysis and for peritoneal dialysis. Another system directed moretowards peritoneal dialysis is depicted in FIG. 4. System 40 includes awater source 41, which may be a municipal water source, or other watersource, or may be a source of spent dialysate. A first filter ortreatment vessel 42 is intended to remove impurities such as describedabove, the filter followed by a first MEMS sensor 43. In thisembodiment, the purified water or dialysis fluid is then routed to asystem 44 for producing dialysis fluid, one embodiment of which isdepicted below in FIG. 6. As noted above, temperature and pressureelements may advantageously be used in preparation of dialysis fluidfrom concentrates. The composition of the resulting dialysis fluid issensed and checked at a second MEMS sensor 43, as the dialysis fluid isrouted to one or more storage containers 45, where the temperature maybe monitored by one or more temperature elements to ensure safe storage.

When the dialysis fluid is needed, it is pumped by pump 46 to aperitoneal dialysis machine 47, and then to and from the patient by acatheter with two lumens, input lumen 471 and output lumen 472. In thisembodiment, the spent dialysate is routed to a reverse osmosis filter48, with the waste routed to a drain. In this embodiment, there are alsofirst and second vessels or filters 49 a, 49 b, which may be used toremove contaminants, as described above, or may be used with ionexchange resins to remove contaminants and add desirable components. Anelectro-deionization process unit may also be used to remove ioniccontaminants. An ultrafilter 49 c is used to filter the solution and toroute waste to the drain. Other embodiments may also be used. MEMSsensors 13, 29 may be used as indicated, such as after the dialysate isreturned from the patient, and after the treatment vessels or filters,and the ultrafilter. MEMS sensors 13, 29 and 43 may be the same or maybe tuned or capable of sensing different species, different ions, ordifferent substances, as desired and as explained above.

FIG. 5 depicts a home hemodialysis system 50 with a water or dialysaterecycling system 52 as described above. System 50 includes an incomingcity water tap 51 to a water or dialysate recycling system 52, whichalso includes a drain 59 for waste water. Fresh dialysis fluid is sentthrough tubing 53 to a storage container S adjacent hemodialysis machineH with dialyzer 54. As is well known to those with skill in dialysisarts, the patient P has a vascular access site 55 for an arterial needleA_(N) and a venous needle V_(N). The patient P is connected to thehemodialysis machine H via tubing 56. Spent dialysis fluid is returnedto the recycling system 52 via tubing 57.

The MEMS sensors 13 described above may be used at several points insystem 50. One or more sensors 13 may be deployed within the dialysaterecycling system 52, for instance, to check on the incoming water fromsource 51 or the returned dialysate from tubing 57. Depending on thewater or dialysis quality, a decision is made whether to send thereturned dialysate to the drain 59 or to reuse the dialysate bycleaning, filtering, and replenishing the dialysate. A second MEMSsensor may be used to monitor the quality and composition of thedialysate sent to, or stored in, dialysis fluid storage container S. Asa third example, another MEMS sensor 13 may be deployed withinhemodialysis machine H to monitor the composition of the returneddialysate or species within the patient's blood. As discussed above,this sensor can help the patient or the caregiver determine whether thedialysis process is changing the appropriate parameters of the blood orthe dialysis fluid, thus giving an indication of whether the therapy isworking as effectively as desired.

A system for preparing dialysis fluid from concentrate using make-upwater or cleansed dialysis fluid is depicted in FIG. 6. One system 60for producing dialysate is depicted in FIG. 6. System 60 receives waterfrom water source 61 and passes the water through one or morepurification vessels 61 a, 61 b, as described above. MEMS sensors 13 areused to sense and report the sensed quantities of impurities or othercomponents of the water as it flows from the first and second vessels.The water passes through control valve 61 c and is heated, if desired,using in-line heater 61 d. The heated water flows through lines 61 e, 61f to A and B concentrate pumps 62, 63, for pumping concentraterespectively from reservoirs 62 a, 63 a. The pumps are positivedisplacement pumps, such as gear pumps, vane pumps, or piston pumps, topump precise amounts of A or B concentrate. One embodiment uses smallceramic piston pumps, available from Fluid Metering, Inc., Long Island,N.Y., U.S.A. Other pumps may be used. Other embodiments useproportioning or ratiometric pumps, whose flow of A or B concentrate maybe set, and which thereafter pump A and B concentrate in a ratioproportional to the water metered out by the pumps.

Other than volumetric ratio, the pumps may be controlled by a feedbackloop that includes a MEMS conductivity monitor. The concentrate pump issped up if the conductivity at the conductivity sensor 64 e is too lowor is slowed if the conductivity at the probe is too high. Since thecharacteristic volumes of the concentrate pumps are known, there arelimits on the amount of cycling needed to produce a stable dialysissolution. A controller for the system keeps track of the amounts ofconcentrate pumped, and also keeps track of the amount of incoming waterand A concentrate that is pumped, thus keeping precisely proportionedflows.

In this embodiment, A concentrate pump 62 pumps A concentrate to mixingvessel 64 through line 62 a, the vessel not filled but retaining an airgap at its top, while the correct ratio of water also flows to thevessel through line 61 f. After the water and the A concentrate aremixed, the mixture is deaerated by spraying using precision meteringpump 64 a, nozzle 64 c, and air trap 64 b. Other embodiments such as asimple restriction creating a starved intake to pump 64 a, could besubstituted for the sprayer to remove the air from the solution. Themixture is monitored by temperature sensor 64 d and MEMS conductivitysensor 64 e. Vessel 64 includes a level sensor L. The deaerated acidmixture is then sent to the B mix chamber 65, where B concentrate fromthe B concentrate pump through line 63 b is added, in this case in-line.

The B mix chamber 65 is equipped with a second MEMS sensor 66 to monitorthe composition of the finished dialysis solution. This sensor can checkthe conductivity of the finished solution, and may also check otherparameters or qualities of the solution. For example, a WaterPoint™ 870Sensor, from Sensicore, Inc., may be used to check several parameters,including conductivity, pH, temperature, total dissolved solids (TDS,based on sodium ions), calcium, magnesium, total hardness, carbonatealkalinity, and other parameters. Many of these are very useful to apatient or to a caregiver preparing dialysis solution, since thesemeasurements are directly related to the quality and make-up of thedialysis solution. As a check, this MEMS sensor can also sense andreport general water quality, such as the concentrations of total andfree ammonia (related to urea in the dialysate), chlorine, andchloramines. Other embodiments may use more than two concentrates, andthe system may be changed to use a separate pump to pull the properamount from each container of concentrate. Any of these systems may thusprepare a customized solution or prescription for each patient. The MEMSsensors may be used to monitor and control the process, as well as thefinal product, in any of these embodiments.

The dialysis solution is then pumped by supply pump 67 through filter 67a, to remove particles larger than 150 micrometers. Control valve 68controls the flow of dialysis solution from system 60. If the correctlevel of continuity has not been achieved, the freshly-prepared dialysissolution may be recycled as desired through the filter and the mixingchamber, as shown, until the proper mixing and purity has been achieved.The dialysis solution can then be pumped through a final filter,endotoxin filter 69, and checked by final MEMS sensor 13 after thefilter, on its way to a storage container or for use. The endotoxinfilter is intended to remove bacteria, such as E. coli and P.aeruginosa, as well as endotoxins. This filter could be an ultrafiltersuch as those made by Medica SRL, Mirandola, Italy, or from Nipro Corp.,Osaka, Japan.

The process described above is only one method for preparing a dialysissolution. Other dialysis solutions may be used, including thoserequiring an osmotic agent, such as a small amount of dextrose, glucose,sodium or potassium polyacrylate, or mixtures of these, or othercomponents. These solutions are prepared in generally similar ways, someembodiments using powders, some using concentrates, some usingsolutions. Any such embodiments, including MEMS sensors, are intended tofall within the scope of the present invention. Embodiments usingpowders may require a conventional stirred-tank vessel, or vesselsuitable for mixing powders using a stirrer or using flow, oftenturbulent flow, to insure a good mixing. For home use, this may be anysuitable mixer capable of maintaining and preserving sterility, whenused with the MEMS sensors described above.

In addition to the MEMS sensors described above, other MEMS sensors arepresently in development and testing. These include MEMS sensors thatare capable of sensing and quantifying organic materials. These sensorswork in the same manner as the other MEMS sensors, but operate bydetecting analytes that are associated with an organic substance ratherthan an inorganic ion, such as ammonium or chlorine. These MEMS sensorsare, or will be, capable of sensing total organic carbon (TOC), and alsospecific substances, such as urea, creatinine, β₂-microglobulin,heparin, and glucose or other sugar or osmotic agent in the dialysisfluid. MEMS sensors could also be used to detect levels of bacteria,endotoxins, and viruses in the water or spent dialysis fluid. Inaddition, MEMS sensors may be used to detect analytes of interest in theblood, such as proteins in general, including albumin, free hemoglobinand hematocrit.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

1. A system for preparing dialysis fluid, comprising: a first purification vessel comprising a purification medium for water; a device for pumping or measuring the water; a heater for heating the water; a mixing chamber configured for receiving the water from the device and for mixing the water with a concentrate to form a fresh dialysis solution; a filter for filtering the fresh dialysis solution; and a microelectromechanical systems (MEMS) sensor placed in fluid communication with an output from a vessel selected from the group consisting of the first purification vessel, the device, the heater, the mixing chamber and the filter.
 2. The system according to claim 1, wherein the MEMS sensor comprises an ion-selective sensor suitable for sensing two or more of an ion selected from the group consisting of ammonium, sodium, calcium, magnesium, potassium, carbonate, bicarbonate, hydrogen or hydronium, hydroxyl, chloramine and chloride.
 3. The system according to claim 1, wherein the MEMS sensor comprises an ion-selective sensor suitable for sensing at least two parameters selected from the group consisting of pH, calcium, total hardness, carbon dioxide and ammonia.
 4. The system according to claim 1, wherein the MEMS sensor is an amperometric sensor suitable for sensing chlorine and chloramines.
 5. The system according to claim 1, wherein the MEMS sensor further comprises a power source and a radio for remote communications.
 6. The system according to claim 1, wherein the water comprises fresh water or a spent dialysis solution.
 7. The system according to claim 1, further comprising a second purification vessel placed downstream of the first purification vessel, the second purification vessel further comprising a purification medium selected from the group consisting of a non-selective purification medium, a selective purification medium, an electro-deionization cartridge and an ion-exchange resin.
 8. The system according to claim 1, further comprising a water pump in operable communication with the first purification vessel or the heater.
 9. The system according to claim 1, wherein the MEMS sensor is suitable for measuring a plurality of substances in an aqueous solution or mixture.
 10. A system for preparing dialysis fluid, comprising: a first purification cartridge comprising a purification medium for water; a heater for heating the water received from the first purification cartridge; first and second pumps for pumping and metering first and second concentrates; a mixing chamber configured for receiving the first and second concentrates from the first and second pumps and for mixing the first and second concentrates with the water to form a fresh dialysis solution; a filter for filtering the fresh dialysis solution; and a microelectromechanical systems (MEMS) sensor placed in fluid communication with an output of a vessel selected from the group consisting of the first purification cartridge, the heater, the mixing chamber and the filter, wherein the MEMS sensor is suitable for sensing at least two substances in a stream selected from the group consisting of water from the first purification cartridge, the fresh dialysis solution and the filtered fresh dialysis solution.
 11. The system according to claim 10, wherein the MEMS sensor further comprises a radio transmitter for communicating with a controller of a dialysis machine.
 12. The system according to claim 10, further comprising an ultrafilter for removing bacteria and microorganisms from the water or from the dialysis solution.
 13. The system according to claim 10, further comprising a reverse osmosis filter for cleaning the water or the dialysis solution.
 14. The system according to claim 10, further comprising an ultraviolet light source for irradiating the water or dialysis solution, the ultraviolet light source placed upstream of the filter.
 15. The system according to claim 10, further comprising an air trap for removing air from the fresh dialysis solution.
 16. The system according to claim 10, wherein the water comprises fresh water or a spent dialysis solution.
 17. A method of preparing dialysis solution, comprising: furnishing a supply of water; purifying the water in at least one pass through a purification medium; heating the water; adding the water to at least one dialysis concentrate to form a dialysis solution; filtering the dialysis solution; and sensing at least two characteristics of the water with a microelectromechanical systems (MEMS) sensor.
 18. The method of claim 17, wherein the MEMS sensor senses using an ion-selective membrane or an amperometric cell.
 19. The method of claim 17, further comprising sensing a characteristic of the dialysis solution with a second MEMS sensor.
 20. The method of claim 17, wherein the purification medium is selected from the group consisting of activated carbon and charcoal.
 21. The method of claim 17, wherein the dialysis solution formed comprises make-up for a spent dialysis solution, and further comprising sensing at least two characteristics of the spent dialysis solution with a MEMS sensor.
 22. The system according to claim 17, wherein the water comprises fresh water or a purified spent dialysis solution.
 23. A method of preparing dialysis solution, comprising: furnishing a supply of water and spent dialysate; purifying the water and the spent dialysate in at least one pass through a purification medium, wherein the purification medium may be in one vessel or more than vessel; heating the water; adding the water and at least one dialysis concentrate to form a dialysis solution; filtering the formed dialysis solution; and sensing at least two characteristics of a stream selected from the group consisting of the water, the formed dialysis solution and the spent dialysis solution with a microelectromechanical systems (MEMS) sensor.
 24. The method of claim 23, further comprising sending a signal from the MEMS sensor to a remote controller.
 25. The method of claim 23, further comprising performing peritoneal dialysis or hemodialysis.
 26. The method of claim 23, further comprising removing air from the formed dialysis solution.
 27. A method of purifying dialysis solution, comprising: furnishing a supply of spent dialysate; purifying the spent dialysate in at least one pass through a purification medium in a vessel to form a purified dialysate; filtering the spent dialysate to form a filtered dialysate; and sensing at least two characteristics of a stream selected from the group consisting of the spent dialysate, the purified dialysate and the filtered dialysate with a microelectromechanical systems (MEMS) sensor.
 28. The method of claim 27, wherein the method is accomplished with a portable dialysis system in which the vessel is a cartridge, and further comprising conducting dialysis while wearing the portable dialysis system.
 29. The method of claim 27, wherein the vessel adsorbs impurities from the spent dialysate and releases desirable ions into the spent dialysate as the spent dialysate passes through the vessel.
 30. The method of claim 27, further comprising making fresh dialysate from water and concentrate and adding the fresh dialysate to the filtered dialysate.
 31. A method for performing dialysis, comprising: providing a dialysis machine and a supply of dialysis fluid; sensing and determining a composition of the dialysis fluid with a MEMS sensor suitable for sensing and detecting at least two ions in the dialysis fluid; performing dialysis on a patient using the dialysis fluid; sensing and determining a composition of the dialysis fluid after the step of performing dialysis with a MEMS sensor; purifying the dialysis fluid after the step of performing dialysis; sensing and determining a composition of the dialysis fluid after the step of purifying with a MEMS sensor; and reusing the dialysis fluid if the composition of the dialysis fluid after the step of purifying is suitable for dialysis.
 32. The method of claim 31, wherein the steps of sensing and determining are conducted with a MEMS sensor comprising an ion-selective sensor suitable for sensing two ions selected from the group consisting of ammonium, sodium, calcium, magnesium, potassium, carbonate, bicarbonate, hydrogen or hydronium, hydroxyl, chloramine and chloride.
 33. The method of claim 31, wherein the MEMS sensor comprises an ion-selective sensor suitable for sensing at least two parameters selected from the group consisting of pH, calcium, total hardness, carbon dioxide and ammonia.
 34. The method of claim 31, wherein the MEMS sensor is an amperometric sensor suitable for sensing chlorine or chloramines.
 35. The method of claim 31, further comprising sending the compositions to a controller of the dialysis machine.
 36. The method of claim 31, wherein the step of conducting dialysis is accomplished with peritoneal dialysis or hemodialysis.
 37. The method of claim 31, wherein the dialysis is hemodialysis and further comprising sensing and determining a composition of blood of a patient with a MEMS sensor. 